Results in previous animal experiments: In the SC (subcutaneous) model, AZD3759 showed comparable efficacy to Tarceva (15 mg/kg) at a dose of 3.75 mg/kg qd. As the dose increased, a more profound tumor regression was observed in AZD3759 treated animals. In the BM (brain transfer) model, the luciferin signal in the brain continued to increase in Tarceva-treated animals and 90% of the animals died during the 60-day study. In contrast, AZD3759 induced a significant tumor regression in the brain and at the end of the study 90% of the animals were still alive without significant weight loss. In the LM (piliar) model, tumor progression was more positive than BM, 80% of animals died within 30 days of the Tarceva group, and AZD3759 induced significant tumor regression in the brain and spinal cord, with 90% of animals surviving over 30 days .

AZD3759 activity in patients

Highly active antitumor activity has also been demonstrated in current human patient clinical trials. As of December 30, 2015, clinical trials recruited 29 patients, 21 with measurable BM, 5 with LM, and 3 with Not Measurable / Non-BM and LM. All patients received at least EGFR targeted therapy and chemotherapy. Of the 29 patients, 17 had prior brain radiation therapy. AZD3759 is tolerated up to 300mg/bid (twice daily) for a maximum treatment time of > 40 weeks.

Of the 20 BM patients evaluated for RECIST, 8 had tumor shrinkage in the brain, 3 were diagnosed with partial remission (PR), and 3 were undiagnosed. In 5 LM patients, after one week of CSF treatment, 3 out of 4 patients had >50% pEGFR inhibition in CSF tumor cells, and 4 out of 5 LM patients had > in cerebrospinal fluid (CSF) > 50% reduction in the number of tumor cells. Tumor cells were cleared in CSF at 300 mg/bid in one LM patient and improved brain MRI imaging and CNS symptoms. Two LM patients were still treated with AZD3759 at doses of 200 mg and 300 mg bid, respectively, after 19 and 29 weeks, respectively.

The progression of tumor progression to brain is particularly common in lung cancer patients. Many lung cancer patients have brain metastases after the development of advanced tumors. However, the situation of brain metastases is particularly difficult in the current medical community. It is difficult for ordinary drugs to penetrate the blood-brain barrier. At present, whole brain radiation therapy is the standard treatment strategy for brain metastases. The side effects of radiotherapy are large, but patients have to accept it. Based on this effective treatment of brain metastases is an urgent need for patients. AstraZeneca's latest listed lung cancer drug targeting drug AZD9291 (Tagrisso, austeni) has this curative effect. AZD9291 is also a fiercely targeted lung cancer drug currently on the market, in addition to its ability to overcome Iressa resistance. Brain metastases can be treated, these are the first generation of lung cancer targeting drugs such as Iressa, Tarceva does not have the effect.

AZD3759 is another EGFR target for lung cancer and a targeted drug for brain metastasis developed by AstraZeneca. AZD3759 is mainly designed to effectively cross the blood-brain barrier to solve non-small-cell lung disease patients with EGFRm + The central nervous system (CNS) metastases such as Brain Metastasis (BM) and LM (Leptomenigeal Metastasis) AZD3759 have now been studied and developed in Phase I/II. It is worth noting that this drug was developed by AstraZeneca China team.

Judging from current clinical trials, AZD3759 first has the basic efficacy of EGFR targeting drugs such as Iressa and Tarceva, with a focus on brain metastases.